The purpose of these investigations is to study the carbohydrate composition of normal and abnormal fibronogen and to define the relationship between the abnormal carbohydrate moiety of the dysfibrinogenemia of liver disease and its functional abnormality. Analysis of the sugar composition of normal and patient fibrinogens will be done by colorometric methods after acid hydrolysis of enzymatic cleavage and also by gas liquid chromatographic methods. The component chains of fibrinogen will be isolated by column chromatography after reduction and carboxymethylation. Glycopeptides will be prepared by Concanavalin A affinity chromatography after enzymatic digestion. The carbohydrate composition of the isolated chains and glycopeptides will be analyzed by gas liquid chromatography, except for sialic acid. Sialic acid will be measured by the thiobarbituric acid method after acid hydrolysis. The effects of stepwise enzymatic cleavage of the peripheral sugar residues on the functional and metabolic properties of normal and test fibrinogens will also be studied. Asialo-agalacto-fibrinogen and asialo-agalacto-ahexosamino-fibronogen will be compared to untreated fibrinogen. Thrombin times of the enzyme-treated fibronogens will be performed and metabolic studies with simultaneous infusion of 125I-enzyme treated fibrinogen and 131I-untreated fibrinogen, with its full carbohydrate complement, will be performed in rabbits and rats. The organ distribution of the radioactivity will also be studied. The results of these studies with enzyme-treated normal fibrinogen will be compared to those of enzyme-treated abnormal fibrinogen which is known to have an increased number of terminal sugar residues. The dysfibrinogenemia of liver disease and fibrinogen Philadelphia will be further characterized by analysis of their individual chains and fragments D and E. The binding affinity of these fragments of "thrombin-treated" fibrinogen conjugated to Sepharose will also be examined.